Intrinsic Breast Tumor Subtypes, Race, and Long-Term Survival in the Carolina Breast Cancer Study

Study Design: Prospective cohort study of patients enrolled in the Carolina Breast Cancer Study (CBCS). Patients were categorized into tumor subtypes based on the expression of estrogen receptor (ER), progesterone receptor (PR), HER2, HER1, and cytokeratin 5/6 (CK5/6) and followed for a median of 9 years for breast cancer death.

Study Eligibility: Invasive breast cancer patients diagnosed from 1993 to 1996 and 1996 to 2001 in the Carolina Breast Cancer Study who had tumor tissue available for subtype analysis.

Enrollment: 1,149 invasive breast cancer patients – 518 African American and 631 white

Research Question: Does survival for breast cancer subtypes differ by race and menopausal status?

African American women experience higher mortality and shorter survival time from breast cancer than white women, and pinpointing why this disparity exists remains an active area of research today. One possible explanation for the poorer prognosis of tumors in African American women may be the higher prevalence of basal-like tumors in these women (especially in younger women) for which we have yet to develop a targeted therapy. In this population-based study, O’Brien et al. explored subtype-specific invasive breast cancer survival differences by race and menopausal status.

The investigators identified invasive breast cancer patients diagnosed from 1993 to 1996 and 1996 to 2001 in the Carolina Breast Cancer Study (CBCS): a population-based case-control study conducted in 24 counties of North Carolina. Of the 1,808 women with breast cancer enrolled in this study, tumor tissue samples were available for 238 premenopausal African Americans, 280 postmenopausal African Americans, 323 premenopausal whites, and 308 postmenopausal whites. Breast tumors were classified into subtypes using 5 immunohistochemical (IHC) markers: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), HER1, and cytokeratin 5/6 (CK 5/6). Tumors were classified as:

luminal A (ER+ and/or PR+, HER2-)
luminal B (ER+ and/or PR+, HER2+)
HER2+, ER-, PR-
Basal-like (ER-, PR-, HER2-, HER1+, and/or CK 5/6+)
unclassified, negative for all five markers

By adding HER1 and CK5/6 to the list of markers used to subtype, the researchers were able to separate “triple-negative” subtypes into basal-like and unclassified cancers. Women were followed for a median of 9 years and were matched to National Death Index-recorded deaths.

The authors found that 64% of whites had luminal A tumors compared to 48% of blacks, and luminal B disease was also more common in whites than blacks with frequencies of 11% and 8%, respectively. On the other hand, basal-like and HER2+/ER- tumors, which had the worst prognosis for all women (poor prognosis for HER2+ tumors because this is the era before Herceptin), were more common in blacks compared to whites. In premenopausal women, 29% of black women had basal-like tumors compared to 15% of white women.

After a median follow-up of 9 years, there were 347 deaths, 239 of which were due to breast cancer. African American women were more likely to die of breast cancer than whites, with a 5-year breast cancer-specific mortality of 17% and 11%, respectively. Although African Americans had higher breast cancer mortality than whites, when the effect of race on subtype-specific mortality was assessed, race was only statistically significant among women with luminal A breast cancer. When compared to the luminal A subtype within race and menopausal status strata, breast cancer-specific mortality for basal-like cancer was highest in postmenopausal white women (HR=3.9, 95% CI=1.4-10.0) and lowest in premenopausal African American women (HR=1.3, 0.8-2.3).

A higher proportion of black women get the worst kinds of cancer. Some thought that breast cancer may be a more aggressive disease in black women; however this study suggests that this is not true. Racial differences in breast cancer mortality were observed for the luminal A subtype, which is more common among white women and has one of the better prognoses. Tamoxifen is an established treatment for luminal A and B cancers, and therefore access to this treatment may also explain some of the mortality disparity between races.

Limitations of this study include small sample size when stratified by IHC subtype, race, and menopausal status, which leads to imprecise effect estimates. Information on treatment patterns was not available in the CBCS, thus leaving the possibility that treatment received may explain some of the observed associations. However, this well-designed study suggests that, contrary to popular belief, race may have little to no effect on prognosis above and beyond marker status (see commentary by Dr. Otis Brawley from the American Cancer Society). <-->

Citations

O’Brien KM, Cole SR, Tse CK, et al. “Intrinsic Breast Tumor Subtypes, Race, and Long-Term Survival in the Carolina Breast Cancer Study.” Clin Cancer Res. 2010 Dec 15;16(24)6100-10. Select ScienceDirect to view article


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